Interstitial or extravascular fluid is the coupling medium between bone matrix and bone cells. Not only is this fluid the perfusate that defines the biochemical environment of the cell, but it has been postulated to play a key role in mechanotransduction, i.e. transmission of mechanical loads incurred during physiological activity from the organ to the tissue to the cellular level. Bone cells are the "micro machines" that remodel the tissue in order to adapt to the prevailing mechanical and biochemical environment. The cues or signals that trigger this cell activity are still poorly understood. Fluid flow is a putative mechanism for remodeling activity associated with bone adaptation in health and disease. This proposal describes the logistical and conceptual plans for a 5th Bone Fluid Flow Workshop to be held in Cleveland. The past decade has been a time of revival for the field of bone fluid flow. The first workshop to review the state of the art and to discuss new developments in the field was held in New York in 1997. The current proposal for the 5th Bone Fluid Flow Workshop seeks funding to support the field at an important crossroads, where the field is on the cusp of translation to the clinic. Although great strides have been made in the past ten years, open questions and gaps in understanding still remain. This has provided the impetus to organize the workshop according to a new paradigm in 2003. The ultimate goals of the 5th Bone Fluid Flow Workshop are threefold. First, similar to previous workshops, recent breakthroughs related to fluid flow through bone will be presented. The second and third goals are unique to this workshop. Second, past assumptions regarding fluid flow through bone will be questioned and explored by addressing parallel phenomena in other biophysical systems and discussion of their implications for bone physiology. Third, critical open questions will be identified; the answers to these questions are expected to push the field into the future, providing a basis for translational research. Our specific aims are to address implications of fluid flow for bone physiology from the organ (Session 1) to the cellular (Session 2) and the subcellular (Session 3) level. Furthermore, implications of fluid flow for tissue engineering (Session 5) and patient care (Session 6) will be addressed. Finally, looking towards the future, we will close the meeting by addressing the potential role of fluid flow in microgravity-induced osteopenia, which is a condition similar to disuse osteopenia and osteoporosis on Earth (Session 7).